1-Hydroxy-9-keto-3-alkyl-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyrans (preferably named as 1-hydroxy-3-alkyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-ones) were synthesized as intermediates by Fahrenholtz, Lurie and Kierstead, J. Am. Chem. Soc., 88, 2079 (1966), 89 5934 (1967) according to the following reaction procedure: a 5-alkyl resorcinol is reacted with diethyl .alpha.-acetylglutarate to form an ethyl 4-methyl-5-hydroxy-7-alkylcoumarin-3-propionate. Cyclization of this lactone ester with a metal hydride yields a tricyclic keto lactone of the following structure (Formula I): ##STR1## Protection of the 9-keto group by ketal formation followed by treatment of the ketal with a methyl Grignard Reagent and subsequent cyclization and removal of the ketal group yields a 1-hydroxy-3-alkyl-6,6-dimethyl-6,6a,7,8-tetrahydro-9H-dibenzo[b,d]pyran-9- one of Formula II below: ##STR2## Reduction of the .DELTA..sup.10(10a) double bond with lithium in liquid ammonia at -78.degree. C. yields predominantly the trans ketone, dl-trans-1-hydroxy-3-alkyl-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-diben zo[b,d]pyran-9-one, Formula III, along with minor quantities of the corresponding 6a,10a cis isomer. ##STR3## No pharmacological activity was reported for this compound and it was used only as an intermediate. Compounds according to Formula III can readily be transformed by treatment with a methyl Grignard Reagent to the corresponding 9-methyl-9-hydroxy compound, dehydration of which yields directly either a .DELTA..sup.8 or .DELTA..sup.9 -tetrahydrocannabinol derivative, the latter being an active constituent of hashish. The Fahrenholtz et al synthesis is also described in U.S. Pat. No. 3,507,885 and in U.S. Pat. No. 3,636,058, a continuation-in-part of the previous patent. (In the Fahrenholtz et al patents, structure VI corresponds to Formula I above, structure VII to Formula II above, and structure III to Formula III above). Although apparently only a single compound of Formula III above was actually prepared by Fahrenholtz (the 3-n-pentyl derivative -- see example 8 of U.S. Pat. No. 3,636,058), a large number of alkyl substituted resorcinols are described, all of which can be used to synthesize other 3-alkyl derivatives of Formula III. Resorcinols named include 5-(1,2-dimethylheptyl)resorcinol, 5-(1-methyloctyl)resorcinol, 5-(1-methylheptyl)resorcinol, 5-(1,2-dimethylbutyl)resorcinol, etc. Petrzilka, U.S. Pat. No. 3,873,576 discloses a different procedure for preparing .DELTA..sup.9 -T.H.C. which utilizes different intermediates from those employed by Fahrenholtz et al. A review article "Problems of Drug Dependence -- Cannabis (Marijuana) Selected Bibliography (1950-1967) prepared by the Medical Literature Branch, Bureau of Medicine, FDA, Department of Health, Education and Welfare, Addendum I, Substances Occurring Naturally in Marijuana, etc., Isbel, (Washington, D.C., 1968)" and an article entitled Recent Advances in the Chemistry of Hashish, Mechoulam and Gaoni, Fortschritte Der Chemie Organicher Naturstoffe, 25, 175 (Springer, Wien, 1957) mention the Fahrenholtz, et al synthesis as well as other synthetic procedures for preparing active tetrahydrocannabinols; no pharmacological activity for compounds having a ketone group at 9 in the dibenzopyran ring system is recorded therein.
Archer, U.S. Pat. No. 3,928,598 discloses the use as anti-anxiety, sedative, analgesic and antidipressant agents of compounds according to Formula IV below.